Laboratory studies will develop methods to examine the reinforcing and discriminative effects of alcohol, caffeine and nicotine in humans, examine the effects of nicotine administration in smokers and nonsmokers, further characterize caffeine and nicotine withdrawal, describe the effects of combining stimulants (e.g. cocaine) and sedatives (e.g. alcohol) and test the effects of drugs on learning, performance and social interaction. Laboratory studies will also examine the influence of environmental, pharmacological, organismic (e.g. behavioral history and genetics) and procedural variables on the reinforcing, discriminative, and direct effects of drugs. Epidemiological studies will longitudinally study the process of smoking cessation in self-quitters, examine the prevalence of DSM-III-R defined caffeine and nicotine disorders, and test the association of nicotine dependence with past and present psychiatric disorders. Treatment studies will test new nicotine replacement and non-nicotine pharmacological treatments for nicotine dependence, as well as behavioral treatments for cocaine and nicotine dependence. Continued funding of the candidate will help develop the Human Behavioral Pharmacology Laboratory and allow the applicant to select only administrative, clinical and teaching activities that are consistent with his career goals and growth of the laboratory.